Neuroprotective and regenerative effects of fibrin sealant derived from snake venom combined with mononuclear stem cells after neurorrhaphy of the sciatic nerve of neonatal rats

• Grant number: 11/23377-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2012
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Benedito Barraviera
• Grantee: Natália Perussi Biscola
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 14/11405-4 - Alpha/gamma motoneuron survival rate and plasticity following neonatal sciatic nerve axotomy, BE.EP.DD

Abstract

The efficient repair in nervous system related lesions is an ancient challenge for Medicine. The use of well-established experimental models allows to evaluate the potential of different treatments in order to prevent the induced changes. The nervous system of neonatal rats is more sensitive to injury, leading to degeneration of spinal motor and sensory neurons. In this regard, the axotomy of the peripheral nerve of these animals represents a special model for the study of agents or techniques that may lead to neuroprotection. After transection of a peripheral nerve, there is a need to reconnect the stumps as they can be reapproximated by several surgical techniques. The fibrin sealant derived from snake venom (the CEVAP´s sealant) has been widely used as adhesive and scaffold. Its application enables the Bone Marrow Mononuclear Stem Cells (BMMSC) associate themselves. Recent studies have shown promising results focusing the implant of these cells as therapy for treatment of central nervous system diseases and injuries, attributing a functional improvement to the local production of trophic factors. Therefore, fibrin sealants appear to be an excellent alternative to stabilization of stem cells applied on site, besides having its adhesive properties. Thus, the aim of this study is to evaluate the neuroprotective and regenerative potential of Bone Marrow Mononuclear Stem Cells (BMMSC) after neurorrhaphy with fibrin sealant on spinal sensory and motor neurons of neonatal rats subjected to sciatic nerve axotomy. The animals are divided into four groups: Group I (n=30): axotomy of the sciatic nerve without treatment; Group II (n=30): axotomy of the sciatic nerve, followed by end-to-side neurorrhaphy with fibrin sealant; Group III (n=30): sciatic nerve axotomy and treatment with BMMSC; Group IV (n=30): axotomy of sciatic nerve, followed by treatment with BMMSC and end-to-side neurorrhaphy with fibrin sealant. It will be used the flow cytometry techniques to characterize the BMMSC; transmission electron microscopy for synaptic plasticity analysis; immunohistochemical to validate the reactive gliosis and determination of locally trophic factors production in vivo by BMMSC. Light microscopy will be used to investigate the neuronal survival; motor tests will be performed to calculate the sciatic functional index and sensorial test to evaluate the nociceptive functional improvement. Finally, it is expected that the fibrin sealant acts on neurorrhaphy by preserving stem cells and promotes their neuroprotection during neuronal regeneration. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; FERREIRA JUNIOR, RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair. NEURAL PLASTICITY, 2016. (12/08101-8, 14/06892-3, 11/23377-7, 11/23236-4, 09/53846-9)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; ULIAN-BENITEZ, SUZANA; BARBIZAN, ROBERTA; CASTRO, MATEUS VIDIGAL; SPEJO, ALINE BARROSO; FERREIRA, JR., RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Multiple uses of fibrin sealant for nervous system treatment following injury and disease. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, n. 1, MAR 14 2017. (12/20456-6, 12/08101-8, 14/06892-3, 12/22750-9, 12/02689-3, 11/23377-7, 11/02889-0, 13/04409-0, 09/53846-9, 14/11405-4, 10/00729-2, 13/23030-2, 12/13514-0)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; FERREIRA JUNIOR, RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair. NEURAL PLASTICITY, v. 2016, p. 19-pg., 2016-01-01. (14/06892-3, 09/53846-9, 12/08101-8, 11/23236-4, 11/23377-7)

NATALIA PERUSSI BISCOLA; LUCIANA POLITTI CARTAROZZI; SUZANA ULIAN-BENITEZ; ROBERTA BARBIZAN; MATEUS VIDIGAL CASTRO; ALINE BARROSO SPEJO; RUI SEABRA FERREIRA JR.; BENEDITO BARRAVIERA; ALEXANDRE LEITE RODRIGUES OLIVEIRA. Multiple uses of fibrin sealant for nervous system treatment following injury and disease. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, 2017-04-27. (11/23377-7, 13/04409-0, 12/08101-8, 12/13514-0, 12/22750-9, 13/23030-2, 11/02889-0, 12/20456-6, 14/06892-3, 09/53846-9, 14/11405-4, 12/02689-3, 10/00729-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BISCOLA, Natália Perussi. Neuroprotective and regenerative effects of fibrin sealant derived from snake venom combined with mononuclear stem cells after repair of the sciatic nerve of neonatal rats. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.